BACKGROUND AND OBJECTIVES: It has been known that the dominant driver of atrial fibrillation (AF) exists in the left atrium (LA) and the incidence of systemic thromboembolism is higher than that of pulmonary thromboembolism in patients with AF. Therefore, we hypothesized that histological and biochemical characteristics of the LA and the right atrium (RA) are different in patients with mitral valvular AF. SUBJECTS AND METHODS: We analyzed the histology and messenger ribonucleic acid (mRNA) or protein expression associated with endothelial function and thrombogenesis in 33 human atrial appendage tissues (20 LA tissues, 13 RA tissues) taken from 25 patients {57.7+/-11.3 years old, 44% males, AF: sinus rhythm (SR)=17:8} with mitral valve disease. We also performed whole mRNA quantification in 8 tissues (both LA and RA tissues from 4 patients) by using next generation sequencing (NGS). RESULTS: 1) The degree of fibrosis (p=0.001) and subendocardial smooth muscle thickness (p=0.004) were significantly greater in the LA than in the RA. 2) More advanced matrix fibrosis was found in the LA of patients with AF than in the LA of patients with SR (p=0.046), but not in the RA. 3) There was no LA-RA difference in protein (Western blot) and mRNA {quantitative real-time polymerase chain reaction (qRT-PCR)} expressions of NF-kappaB, 3-NT, CD31, E-selectin, inducible NO synthase, stromal cell-derived factor-1alpha, Endothelin-1, platelet-derived growth factor, myeloperoxidase, or NCX, except for higher mRNA expression of HCN4 in the RA (qRT-PCR, p=0.026) and that of KCNN1 in the LA (NGS, p=0.016). CONCLUSION: More advanced matrix and subendocardial remodeling were noticed in the LA than in the RA in patients with mitral valvular AF. However, the expressions of tissue factors associated with thrombogenesis were not significantly different between the RA and the LA.
Atrial Appendage ; Atrial Fibrillation* ; Chemokine CXCL12 ; E-Selectin ; Endothelin-1 ; Fibrosis ; Heart Atria* ; Humans ; Incidence ; Male ; Mitral Valve ; Muscle, Smooth ; NF-kappa B ; Nitric Oxide Synthase ; Peroxidase ; Platelet-Derived Growth Factor ; Pulmonary Embolism ; Real-Time Polymerase Chain Reaction ; RNA ; RNA, Messenger ; Thromboembolism ; Thromboplastin

Purpose: This study aimed to compare the clinical characteristics of patients who showed structural progression in the peri-papillary retinal nerve fiber layer (RNFL) first against those who showed progression in the macular ganglion cell-inner plexi-form layer (GCIPL) first and to investigate clinical parameters that help determine whether a patient exhibits RNFL or GCIPL damage first. Methods: A retrospective review of medical records of patients diagnosed with early-stage normal-tension glaucoma was performed. All eyes underwent intraocular pressure measurement with Goldmann applanation tonometer, standard auto-mated perimetry, and Cirrus optical coherence tomography at 6-month intervals. Structural progression was determined using the Guided Progression Analysis software. Blood pressure was measured at each visit. Results: Forty-one eyes of 41 patients (mean age, 52.6 ± 16.7 years) were included in the study. In 21 eyes, structural pro-gression was first detected in the RNFL at 54.2 ± 14.8 months, while structural progression was first observed at the macular GCIPL at 40.5 ± 11.0 months in 20 eyes. The mean intraocular pressure following treatment was 13.1 ± 1.8 mmHg for the RNFL progression first group and 13.4 ± 1.8 mmHg for the GCIPL progression first group (p = 0.514). The GCIPL progression first group was older (p = 0.008) and had thinner RNFL at baseline (p = 0.001). The logistic regression analyses indicated that both age and follow-up duration until first progression predicted the region of structural progression (odds ratio, 1.051; 95% confidence interval, 1.001–1.105;p= 0.046 for age; odds ratio, 0.912; 95% confidence interval, 0.840–0.991; p = 0.029 for time until progression). Conclusions Age of glaucoma patients and time until progression are associated with the region of the first structural pro-gression in normal-tension glaucoma. Further studies exploring the association between glaucomatous progression and the location of damage are needed.

Purpose: To evaluate the effect of intraoperative mitomycin C (MMC) on the surgical outcomes of ciliary sulcus (CS) Ahmed glaucoma valve (AGV) tube placement. Methods: A retrospective review of medical records of 54 consecutive patients who underwent AGV implantation with tube placed in CS was performed. Consecutive cases operated without the use of intraoperative MMC from 2017 to 2019 were compared with consecutive cases operated with MMC from 2019 to 2021. Surgical failure was defined as intraocular pressure (IOP) exceeding 21 mmHg in two consecutive visits after postoperative 3 months or ≤30% IOP reduction, IOP ≤5 mmHg in two consecutive visits, or loss of light perception. Kaplan-Meier survival analysis and log-rank test were performed to compare the surgical failure rates. Results: A total of 54 eyes of 54 patients were investigated. Mean follow-up period after AGV implantation was 1.4 ± 0.8 years. The MMC group showed significantly lower IOP during the 1st postoperative month (20.5 ± 8.6 mmHg vs. 15.8 ± 6.4 mmHg, p = 0.027), but the difference did not persist 6 months after the surgery (p = 0.805). The mean number of postoperative antiglaucoma medications was significantly lower in the MMC group in the 1st postoperative month (p = 0.047) but no difference was found at 6 months. No statistical difference was noted in the rates of postoperative complications. Kaplan-Meier survival analysis showed comparable survival rates between MMC group and no MMC group (p = 0.356). Conclusions The intraoperative use of MMC significantly lowered IOP in the 1st postoperative month but did not increase 6 months success rates in patients receiving AGV tube placement in CS.

PURPOSE: Recently, mitochondrial DNA 4977bp deletion (mtDNA4977-mut), a somatic mutation related to oxidative stress, has been shown to be associated with atrial fibrillation (AF). We hypothesized that patient age, as well as electroanatomical characteristics of fibrillating left atrial (LA), vary depending on the presence of mtDNA4977-mut in peripheral blood among patients with non-valvular AF. MATERIALS AND METHODS: Analyzing clinical and electroanatomical characteristics, we investigated the presence of the mtDNA4977-mut in peripheral blood of 212 patients (51.1+/-13.2 years old, 83.5% male) undergoing catheter ablation for non-valvular AF, as well as 212 age-matched control subjects. RESULTS: The overall frequency of peripheral blood mtDNA4977-mut in patients with AF and controls was not significantly different (24.5% vs. 19.3%, p=0.197). When the AF patient group was stratified according to age, mtDNA4977-mut was more common (47.4% vs. 20.0%, p=0.019) in AF patients older than 65 years than their age-matched controls. Among AF patients, those with mtDNA4977-mut were older (58.1+/-11.9 years old vs. 48.8+/-11.9 years old, p<0.001). AF patients positive for the mtDNA mutation had greater LA dimension (p=0.014), higher mitral inflow peak velocity (E)/diastolic mitral annular velocity (Em) ratio (p<0.001), as well as lower endocardial voltage (p=0.035), and slower conduction velocity (p=0.048) in the posterior LA than those without the mutation. In multivariate analysis, E/Em ratio was found to be significantly associated with the presence of mtDNA4977-mut in peripheral blood. CONCLUSION: mtDNA4977-mut, an age-related somatic mutation detected in the peripheral blood, is associated with advanced age and electro-anatomical remodeling of the atrium in non-valvular AF.
Adult ; Aged ; Atrial Fibrillation/blood/*genetics/*physiopathology ; Atrial Remodeling/*genetics ; Base Pairing/*genetics ; Case-Control Studies ; DNA, Mitochondrial/*blood/*genetics ; Female ; Heart Atria/pathology/physiopathology ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Mutation Rate ; Phenotype ; Sequence Deletion/*genetics

BACKGROUND AND OBJECTIVES: Although electrical cardioversion (CV) is effective in restoring sinus rhythm (SR) in patients with atrial fibrillation (AF), AF frequently recurs in spite of antiarrhythmic medications. We investigated the predictors of failed CV and AF recurrence after successful CV. SUBJECTS AND METHODS: In 81 patients (M:F=63:18, 59.1+/-10.5 years old) with AF who underwent CV, clinical findings and pre-CV serologic markers were evaluated. RESULTS: During 13.1+/-10.6 months of follow-up, 8.6% (7/81) showed failed CV, 27.16% (22/81) showed early recurrence atrial fibrillation (ERAF; < or =2 weeks), 32.1% (26/81) had late recurrence atrial fibrillation (LRAF; >2 weeks), and 32.1% (26/81) remained in SR and had no recurrence (NR). Plasma levels of transforming growth factor beta (TGF)-beta were significantly higher in patients with failed CV than in those with successful CV (p=0.0260). Patients in whom AF recurred were older (60.4+/-9.0 years old vs. 55.3+/-12.5 years old, p=0.0220), and had lower plasma levels of stromal cell derived factor (SDF)-1alpha (p=0.0105). However, there were no significant differences in these parameters between ERAF patients and LRAF patients. CONCLUSION: Post-CV recurrence commonly occurs in patients aged >60 years and who have low plasma levels of SDF-1alpha. High plasma levels of TGF-beta predict failure of electrical CV.
Aged ; Atrial Fibrillation ; Chemokine CXCL12 ; Electric Countershock ; Follow-Up Studies ; Humans ; Plasma ; Recurrence ; Stromal Cells ; Transforming Growth Factor beta