Associations Between Cardiac Fibrosis and Permanent Atrial Fibrillation in Advanced Heart Failure

Abstract

<jats:p>Atrial fibrosis is considered as the basis in the development of long-standing atrial fibrillation (AF). However, in advanced heart failure (HF), the independent role of fibrosis for AF development is less clear since HF itself leads to atrial scarring. Our study aimed to differentiate patients with AF from patients without AF in a population consisting of patients with advanced HF. Myocardial samples from the right atrial and the left ventricular wall were obtained during heart transplantation from the explanted hearts of 21 male patients with advanced HF. Long-standing AF was present in 10 of them and the remaining 11 patients served as sinus rhythm controls. Echocardiographic and hemodynamic measurements were recorded prior to heart transplantation. Collagen volume fraction (CVF), transforming growth factor-beta (TGF-β), and connective tissue growth factor (CTGF) expression in myocardial specimens were assessed histologically and immunohistochemically. The groups were well matched according to age (51.9±8.8 vs. 51.3±9.3 y) and co-morbidities. The AF group had higher blood pressure in the right atrium (13.6±7.7 vs. 6.0±5.0 mmHg; p=0.02), larger left atrium diameter (56.1±7.7 vs. 50±5.1 mm; p=0.043), higher left atrium wall stress (18.1±2.1 vs. 16.1±1.7 kdynes/m2; p=0.04), and longer duration of HF (5.0±2.9 vs. 2.0±1.6 y, p=0.008). There were no significant differences in CVF (p=0.12), in CTGF (p=0.60), and in TGF-β expression (p=0.66) in the atrial myocardium between the two study groups. In conclusions, in advanced HF, atrial fibrosis expressed by CVF is invariably present regardless of occurrence of AF. In addition to atrial wall fibrosis, increased wall stress might contribute to AF development in long-standing AF.</jats:p>

Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm

“…Fibrosis is considered by many authors as a hallmark of structural remodeling in AF [ 13 – 16 ] and can also cause remodeling of infiltrating subepicardial fatty infiltrates [ 35 ]. However, there are also reports, where no statistical difference in collagen volume fraction or fibrosis was found between AR and SR group of patient most likely due to a variable influence of accompanying structural heart diseases [ 27 , 29 , 32 , 36 , 37 ]. The largest immune cell population was formed by CD68-KP1+ cells of monocyte/macrophage lineage corresponding largely to dendritic cells, which were immunoreactive to DC-SIGN.…”

“…In the present study, we were not able to detect active (acute) myocarditis according to current criteria [ 30 , 31 ]. It seems likely that an elevated number of CD3+ and CD68-KP1+ cells in the left atrial myocardium of patients with AF reflects certain level of inflammatory activation of myocardial tissue due to the mechanical stress accompanying the atrial dilation [ 32 , 33 ]. Expression of inflammatory cytokines is another parameter of local inflammatory state.…”

Looking into a Conceptual Framework of ROS–miRNA–Atrial Fibrillation

“…However, we do not believe that endogenous ROS reach such high levels frequently [ 141 , 142 ], and more importantly, the etiology of AF in humans is more complicated than simply being driven by a single factor, such as ROS. In fact, other factors, such as inflammation and myocardial fibrosis, are also known to promote AF in humans [ 143 , 144 ]. Thus, in our opinion, endogenous oxidative stress most likely acts both as one of the AF triggering factors and as a factor exacerbating AF.…”

Assessment of myocardial viability using a minimally invasive laser Doppler flowmetry on pig model

“…The physiological assessment of myocardial tissue and scar tissue can be critically important for cardiac procedures such as the surgical treatment of ventricular and supraventricular arrhythmias. 4,18 To meet this clinical need, several catheter-based minimally invasive methods, such as intracardiac echocardiography, optical coherence tomography and photoacoustic, are being developed. [19][20][21][22][23] The laser Doppler technique presented in this paper has been evaluated in an in vivo animal model.…”