Characteristics of coronary artery disease among patients with atrial fibrillation compared to patients with sinus rhythm

Background: With a high prevalence of coronary artery disease (CAD) among patients with atrial fibrillation (AF), CAD is one of the main risk factors for AF. However, little is known about the characteristics of CAD in AF patients, especially whether a specific anatomical distribution of coronary artery stenoses might predispose an individual to AF via atrial ischemia remains speculative. To address this issue, we evaluated the potential associations between angiographic characteristics of CAD and AF. Methods: In this single-center retrospective analysis, 796 consecutive patients with confirmed CAD and AF (CAD-AF) and 785 patients with CAD and sinus rhythm (CAD-SR) were enrolled. Clinical characteristics and angiographic findings were compared between groups in stable CAD and during acute myocardial infarction (MI). Results: Mitral valve disease and chronic heart failure were significantly more common in CAD-AF than in CAD-SR. Clinical condition in CAD-AF was significantly more severe as indicated by New York Heart Association/World Health Organization functional class. Left ventricular ejection fraction was reduced in CAD-AF, reflecting the marked fraction of patients with ischemic cardiomyopathy. No association between anatomical characteristics of CAD and AF was found. However, CAD-AF seemed to be associated with a higher CAD severity (p = 0.06). Additionally, CAD-AF with MI showed a significantly higher number of diseased coronary vessels. Conclusion: The anatomical distribution of coronary artery stenoses does not contribute to AF in CAD patients. However, AF is linked to a higher CAD severity, which might predispose individuals to AF by driving ischemic heart disease and changes in left ventricular function

Lymphatic Markers in the Adult Human Choroid

PURPOSE. Reports of lymphatics in the posterior human uvea are contradictory. We systematically analyzed the choroid by combining various lymphatic markers, following recently established guidelines for the immunohistochemical detection of ocular lymphatics. METHODS. Human choroids were prepared for flat mount serial cryosectioning. Sections were processed for immunohistochemistry of the lymphatic markers LYVE-1, PDPN, PROX1, FOXC2, VEGFR3, CCL21, and combined with alpha-smooth muscle-actin and 40,6-diamidino-2-phenylendole (DAPI). Single, double, and triple marker combinations were documented using confocal microscopy. Messenger RNA analysis for CCL21, FOXC2, LYVE-1, PDPN, PROX, and VEGFR3 was performed in choroid and skin. RESULTS. In the choroid, CCL21 immunoreactivity was detected in choroidal blood vessels, intrinsic choroidal neurons, and numerous small cells of the choroidal stroma. These small cells were not colocalized with PROX1 and PDPN, while a subpopulation of cells showed immunoreactivity for CCL21 and LYVE-1, and very occasionally PDPN-only+ cells were detected. Nuclei positive for PROX1 were never detected in the choroid, and vessel-like structures immunoreactive for LYVE-1, PDPN, or CCL21 (other than blood vessels) were never observed. Immunoreactivity of VEGFR3 was absent in the majority of choroidal blood vessels, but present in choriocapillaris, while other structures positive for VEGFR3 were not detected. Nonvascular smooth muscle cells were lacking VEGFR3-immunoreactivity. Messenger RNA analysis detected all lymphatic markers investigated and confirmed immunohistochemical results. CONCLUSIONS. By combining several lymphatic markers, single cells expressed these markers, but classical lymphatic vessels were not detected in the human choroid. Therefore, the healthy adult human choroid must be considered alymphatic, at least with the markers applied here

Topography of Lymphatic Markers in Human Iris and Ciliary Body

PURPOSE. Reports of lymphatics in the anterior human uvea are contradictory. This might be caused due to a certain topography, which has not been considered yet. Therefore, here we systematically analyze iris and adjacent ciliary body with immunohistochemistry by combining various lymphatic markers. METHODS. Human iris and ciliary body were obtained from cornea donors and prepared for cryosectioning. Cross sections of tissue blocks at 12/3/6/9 o'clock position and at corresponding intersections (1:30/4:30/7:30/10:30) were processed for immunohistochemistry of LYVE-1, PDPN, PROX1, FOXC2, VEGFR3, and CCL21, and when necessary, these lymphatic markers were combined with CD31, alpha-smooth muscle-actin, CD68, and 4',6-diamidino-2 phenylindole dihydrochloride (DAPI). Double, triple, and quadruple marker combinations were documented using confocal microscopy. RESULTS. Numerous podoplanin+ cells were mainly located at the anterior border of the iris while LYVE-1+ cells were distributed throughout the nonpigmented part. Both cell populations were PROX1/FOXC2/CCL21/VEGFR3-. Blood vessels, iris smooth muscles, and individual cells were VEGFR3+. While PDPN+ cells were rarely detected posteriorly of the iris root, many LYVE1+ cells were present within the ciliary body muscle and villi. Within the muscle, occasionally PDPN+ vessel-like structures were detectable, but these were never colocalized with LYVE-1. Similar vessel-like structures were VEGFR3+/PROX1-/CCL21-, but CD31+. Further, ciliary muscle fibers and ciliary epithelium were immunoreactive for VEGFR3/CCL21, but were LYVE1/PDPN-. A certain topography of structures at the various uvea-positions investigated was not obvious. The majority of LYVE-1+ cells displayed immunoreactivity for CD68. CONCLUSIONS. Lymphatic vessels colocalizing for at least two lymphatic markers were not detectable. Therefore, if present, putative lymphatic channels of the anterior uvea might display a different marker panel than generally presumed