Abstract
BackgroundThe objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome.MethodsVoluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry.ResultsA total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16−). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio).ConclusionAtrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management.
Highlights
The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome
In this study we examine the link between inflammation and Atrial Fibrillation (AFib) by studying inflammatory cells in the human atrium that are determinant to development of AFib
The recovery rate of the peripheral blood mononuclear cells (PBMC) isolation used was 18.91 ± 2.33% with a total of 0.66 × 106 ± 0.25 CD45+ cells per gram of tissue were found in purified isolates from the atrium representing 18.9% of the total cells isolated per gram of atrial tissue (Fig. 1b(i, ii))
Summary
The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome. Atrial Fibrillation (AFib) is an irregular heart rhythm that affects ~ 1.5% of the population globally (~ 10% adults over 80 years of age), can lead to heart failure or Aguiar et al J Transl Med (2019) 17:413 stroke, and is a major determinant in patient quality of life [1, 2]. Dofetilide) through rate and rhythm control strategies. This approach has limited long-term utility, and additional therapeutic modalities require ablative or surgical maze procedures to physically redirect/control electrical current flow. These approaches can fail to fully resolve AFib. The ultimate goal of treatment is to reduce the likelihood of more catastrophic events The ultimate goal of treatment is to reduce the likelihood of more catastrophic events (ex. thromboembolic stroke) by using anticoagulation therapy, and to reduce myocardial demand (ex. beta blockers)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call