Mien-g Chen

Increased Inflammatory Cell Infiltration in the Atrial Myocardium of Patients With Atrial Fibrillation

Atrial fibrillation (AF) may be caused by structural and electrophysiological changes in the atria induced by inflammation. This study analyzed 35 adult patients with symptomatic severe mitral valve disease and moderate-to-severe tricuspid valve disease and without coronary artery disease who underwent valve operations for congestive heart failure; 18 patients had persistent AF and 17 patients had no history or electrocardiogram examination of AF before surgery. Atrial appendageal tissues obtained during surgery were evaluated for histopathological changes. The number of inflammatory cells identified as CD45-positive cells in the right atrial myocardium in the AF group (7.5 +/- 7.5 cells per high power field) was significantly higher than that of normal controls (2.7 +/- 1.5 cells per high power field, p = 0.0018). The number of inflammatory cells in the right atrial myocardium did not differ between the sinus group and normal controls (2.7 +/- 1.5 vs 2.6 +/- 2.2 cells per high power field, p >0.05). Additionally, the number of inflammatory cells in the atrial myocardium did not differ between the right and left atria in patients with AF (7.5 +/- 7.5 cells per high power field for right atria vs 7.1 +/- 4.2 cells per high power field for left atria, p = 0.7563). Moreover, correlation analysis revealed a significant association between the number of inflammatory cells in the right atrial myocardium and the number of inflammatory cells in the left atrial myocardium in patients with AF (r = 0.6145, p = 0.0067). In conclusion, inflammatory cell infiltration increases in the atrial myocardium of patients with AF.

Long-term outcome and short-term survival of patients with systemic lupus erythematosus after bacteraemia episodes: 6-yr follow-up

OBJECTIVEnTo describe the nature of bacteraemia in SLE patients and determine the short-term survival and long-term outcome of these patients.nnnMETHODSnAnalysis of the medical records of 1442 SLE patients who were regularly followed up in a tertiary teaching medical centre from 2000 to 2005.nnnRESULTSnAmong 1442 SLE patients, 240 patients (17%) developed at least one episode of bacteraemia, corresponding to an incidence of 92.7 cases/1000 hospital admissions. Since SLE diagnosis, the overall survival of our patients was 92% at 5 yrs, 86% at 10 yrs and 79% at 15 yrs. However, after one episode of bacteraemia, the survival decreased to 76% at 30 days and 67% at 360 days. Of the 336 episodes of bacteraemia, 167 were community-acquired (49.7%) and 169 were nosocomial (50.3%). Staphylococcus aureus was the leading cause of Gram-positive bacteraemia. Among Gram-negative bacteria, non-typhoidal Salmonella and Escherichia coli were the most common species. Community-acquired Salmonella and Streptococcus bacteraemia were more common than nosocomial infections. Klebsiella and Acinetobacter spp. were significantly more responsible for nosocomial than community-acquired bacteraemia. Patients infected with Acinetobacter, Klebsiella or Pseudomonas had lower probabilities of 14-day survival (71.4, 55.6, 42.9%, respectively).nnnCONCLUSIONSnAmong SLE patients, an episode of bacteraemia was associated with an unfavourable long-term outcome. The bacterial species significantly influenced short-term survival. Therefore, when empiric antibiotic therapy is initiated in SLE patients who are suspected of bacteraemia, we suggest use of antibiotics that are effective against Pseudomonas, Klebsiella, Acinetobacter, S. aureus, and E. coli.

Atrial myocardial nox2 containing NADPH oxidase activity contribution to oxidative stress in mitral regurgitation: potential mechanism for atrial remodeling

BACKGROUNDnOxidative stress is linked with several cardiovascular diseases. However, the NADPH oxidase activity in severe mitral regurgitation patients with and without atrial fibrillation has not yet been explored.nnnMETHODSnThis study involved 16 adult patients (eight patients with persistent atrial fibrillation and eight with sinus rhythm) with severe mitral and moderate-to-severe tricuspid regurgitation and five control patients without mitral and tricuspid disease. Atrial tissues of the right and left atrial appendages were obtained during surgery. Superoxide anion production was measured by lucigenin-enhanced chemiluminescence, and the expression of nox2 containing NADPH oxidase mRNA was measured by quantitative real-time RT-PCR. Additionally, immunohistochemical study was performed.nnnRESULTSnNADPH-stimulated superoxide release was significantly higher than basal superoxide production from right [5671.9±3498.7 vs. 232.7±70.0 relative light units per second per milligram of protein (RLU s(-1) mg protein(-1)), P=.008) and left atrial homogenates (6475.1±1890.8 vs. 229.0±79.6 RLU s(-1) mg protein(-1), P=.008) in atrial fibrillation patients. The NADPH-stimulated superoxide release from right atrial homogenates was also significantly higher than basal superoxide production in sinus patients (6809.1±1327.1 vs. 244.2±65.5 RLU s(-1) mg protein(-1), P=.008). Additionally, there was a borderline significant correlation between NADPH-stimulated superoxide production from left atrial homogenates and left atrial sizes (r=0.683, P=.062) in atrial fibrillation patients. Membrane-bound nox2 containing NADPH oxidase mRNA expression was increased and was similar in both the atrial fibrillation patients and sinus patients. The NADPH-stimulated superoxide production in right atrial homogenates in control atrial samples was 1863.7±137.2 RLU s(-1) mg protein(-1). Immunohistochemical study demonstrated increased expression of nox2 in myocytes with moderate-to-severe myolysis and hypertrophy.nnnCONCLUSIONSnResults of this study demonstrate that membrane-bound nox2 containing NADPH oxidase activity and expression in the atrial myocardium is increased in patients with severe mitral regurgitation, possibly contributing to atrial remodeling in this clinical setting.

Interleukin-18: a strong predictor of the extent of coronary artery disease in patients with unstable angina

The aim of this study was to confirm that plasma interleukin (IL)-18 level is associated with the extent of coronary artery disease in unstable angina patients. Previous studies have shown that patients with unstable angina have significantly higher plasma IL-18 levels than healthy volunteers. However, the association between IL-18 and the extent of coronary artery atherosclerosis in patients with unstable angina remains unclear. Plasma concentrations of IL-18 and high-sensitivity C-reactive protein (hs-CRP) were measured in 166 consecutive patients admitted for coronary arteriography. One hundred and eighteen patients with unstable angina had coronary artery disease (coronary artery disease group; severity score: 2.32 ± 1.47; Gensini score: 31.3 ± 25.9), and 48 patients with coronary risk factors and without coronary artery lesions served as the risk control group. Plasma levels of IL-18 were higher in the coronary artery disease group than in the risk control group (P = 0.062). Additionally, plasma levels of IL-18 were significantly higher in 77 coronary artery disease patients with severity score ≥2 than in the risk control group (242.3 ± 110.6 vs 209.8 ± 120.3u2009pg/ml, P = 0.016). By univariate analysis, log-transformed plasma IL-18 concentration was positively correlated with coronary artery disease severity score (r = 0.244, P = 0.009). By multiple regression analyses, the association between coronary artery disease severity score and IL-18 remained significant (β = 0.733, P = 0.017) when controlling for age, diabetes mellitus and left ventricular ejection fraction. Additionally, coronary artery disease severity score was greater in the highest tertile (>246u2009pg/ml) of plasma IL-18 levels than in the middle (176–246u2009pg/ml) and the lowest (<176u2009pg/ml) tertiles (2.79 ± 1.52 vs 2.05 ± 1.08 vs 2.13 ± 1.66, P = 0.028). Of note, plasma hs-CRP level had no significant correlation with coronary artery severity. Plasma IL-18 level is associated with the extent of coronary artery disease in unstable angina patients, suggesting the link between IL-18 and coronary artery atherosclerosis in these patients.

Autophagy as a mechanism for myolysis of cardiomyocytes in mitral regurgitation

Eur J Clin Invest 2011; 41 (3): 299–307

Dedifferentiation of atrial cardiomyocytes in cardiac valve disease: unrelated to atrial fibrillation.

BACKGROUNDnValvular heart disease has become an important public health concern. The increased wall stress and underlying disease entity associated with mitral valve disease provide unfavorable circumstances for atrial cardiomyocytes. The expression of the alpha-smooth muscle actin isoform is considered characteristic of cardiomyocyte dedifferentiation (embryonic cardiomyocyte), and cardiomyocyte dedifferentiation may indicate an adaptive state, enabling cardiomyocytes to survive despite unfavorable circumstances.nnnMETHODSnThis study comprised 20 adult patients with symptomatic severe mitral valve disease and moderate to severe tricuspid valve disease and without coronary artery disease undergoing valve operations for congestive heart failure. Ten patients had persistent atrial fibrillation and 10 patients had never been in atrial fibrillation by history and electrocardiograms before surgery. Atrial tissues of the right atrial appendage were obtained during surgery.nnnRESULTSnImmunohistochemical study demonstrated that alpha-smooth muscle actin protein expression was not altered by atrial fibrillation, and alpha-smooth muscle actin protein expression in atrial tissues was higher in patients with sinus rhythm than in those with atrial fibrillation (the percentage of cells that were alpha-smooth muscle actin-positive was 51.5+/-34.9% for right atria from patients in sinus rhythm vs. 16.2+/-15.0% for right atria from patients with atrial fibrillation) (P<.03). Semiquantitation of alpha-smooth muscle actin by immunoblotting of extracts from atrial tissues showed similar findings as in the immunohistochemical observations: that is, atrial fibrillation did not influence the expression of alpha-smooth muscle actin protein. Interstitial fibrosis represented 43.2+/-13.9% of the right atrial tissue in the sinus group, whereas interstitial fibrosis comprised 49.8+/-8.2% of the right atrial tissue in the atrial fibrillation group (P=.320).nnnCONCLUSIONSnDedifferentiation of atrial cardiomyocytes occurs in patients with cardiac valve disease, even without atrial fibrillation.

DNA repair in TUNEL-positive atrial cardiomyocytes of mitral and tricuspid valve diseases: Potential mechanism for preserving cardiomyocytes

BACKGROUNDnThe reported presence of DNA breaks, based on a positive reaction to the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) assay, in fibrillating human right atria of cardiac valve disease may suggest apoptotic myocyte death. However, TUNEL positivity may reflect conditions other than cell death.nnnMETHODSnThis study comprised 27 adult patients (14 patients with persistent atrial fibrillation and 13 in sinus rhythm) with significant mitral and tricuspid valve diseases. Atrial tissues were obtained during surgery.nnnRESULTSnImmunohistochemical study demonstrated that 31.1±12.2% of the myocytes had TUNEL-positive nuclei in the fibrillating right atria whereas 37.4±23.2% of the myocytes had TUNEL-positive nuclei in the right atrial myocardium in sinus rhythm (p=0.505). However, most nuclei of TUNEL-positive myocytes in the right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair but never Ki-67, a replication-associated antigen (TUNEL(+)/PCNA(+) vs. TUNEL(+)/PCNA(-), 30.5±10.8% vs. 1.2±1.5%, p=0.005, in the atrial fibrillation group and 32.8±18.6% vs. 4.6±8.1%, p=0.003, in the sinus group), suggesting that most TUNEL-positive myocytes were undergoing DNA repair. In addition, the incidence of TUNEL-positive myocytes significantly and positively correlated with the incidence of PCNA-positive myocytes (r=0.5, p<0.03 in the right atria; r=0.661, p<0.04 in the left atria).nnnCONCLUSIONSnCell death by apoptosis occurs in a small percentage of atrial cardiomyocytes in mitral and tricuspid valve diseases and DNA repair is more important and preserves the cardiomyocytes.

Relationship of the percentage of circulating endothelial progenitor cell to the severity of coronary artery disease

Previous study demonstrated that the percentage of circulating endothelial progenitor cells was reduced in patients with coronary artery disease. However, the relationship of the percentage of circulating endothelial progenitor cells to the severity of coronary artery disease has not been investigated. The percentages of circulating endothelial progenitor cells were measured in 78 consecutive patients with unstable angina, as well as in 32 healthy volunteers. Dual-stained cells expressing CD34 and vascular endothelial growth factor receptor-2 were judged to be endothelial progenitor cells and were analyzed using flow cytometry. On stepwise multiple linear regression analysis, the percentages of circulating endothelial progenitor cells were independently decreased in patients with unstable coronary artery disease compared with those in the healthy volunteers (P < 0.05). Among patients with unstable coronary artery disease, the percentage of patients with at least one occluded vessel was significantly higher in patients with multi-vessel disease than in patients with single-vessel disease (P < 0.04). On stepwise multiple linear regression analysis, the percentages of circulating endothelial progenitor cells were independently decreased in patients with multi-vessel coronary artery disease compared with those in patients with single-vessel coronary artery disease (P < 0.03). Among patients with unstable coronary artery disease, the percentage of circulating endothelial progenitor cells was significantly related to the severity of coronary artery disease.

Increased serum oxidative stress in patients with severe mitral regurgitation: A new finding and potential mechanism for atrial enlargement

OBJECTIVEnThe aim of this study was to examine the serum oxidative stress in patients with severe mitral regurgitation.nnnDESIGN AND METHODSnThis study analyzed serum oxidative stress index in patients with severe mitral regurgitation [persistent atrial fibrillation (AF) or sinus rhythm], paroxysmal lone AF patients and healthy subjects.nnnRESULTSnThe serum oxidative stress index was significantly higher in the mitral regurgitation AF group and sinus group than in the lone AF group and healthy subjects (p<0.0001). Left atrial size was significantly larger in the mitral regurgitation AF group and sinus group than in the lone AF group and healthy subjects (p<0.0001). The oxidative stress index significantly and positively correlated with left atrial size in the overall study population (r=0.439, p=0.0008).nnnCONCLUSIONSnThis study provides new evidence of increased oxidative stress in human severe mitral regurgitation, probably contributing to atrial enlargement.

Peripheral arterial disease and atrial fibrillation and risk of stroke, heart failure hospitalization and cardiovascular death: A nationwide cohort study

BACKGROUNDnPeripheral arterial disease (PAD) and atrial fibrillation (AF) share several comorbidities and contribute to similar cardiovascular (CV) outcomes. Only few studies have evaluated the correlation between PAD, AF, and their interaction effects on CV outcomes.nnnMETHODSnWe included 597,164 adults from Taiwans National Health Insurance Research Database to conduct a cohort study to assess whether PAD was an independent risk factor of AF and vice versa. We also examined if PAD and AF increased the incident stroke, heart failure hospitalization and CV death.nnnRESULTSnPeople with PAD had a significant higher risk of incident AF than those without PAD [adjusted hazard ratio (HR): 1.29, 95% confidence interval (CI): 1.17-1.42]. Meanwhile, people with AF did not have an increased risk of incident PAD compared to those without AF (adjusted HR: 1.00, 95% CI: 0.89-1.11). Both AF and PAD increased the risk of stroke [adjusted HR being 1.29 (95% CI: 1.17-1.43) and 1.41 (95% CI: 1.35-1.47), respectively], heart failure hospitalization [adjusted HR being 1.96 (95% CI: 1.77-2.17) and 1.35 (95% CI: 1.28-1.42), respectively], and CV death [adjusted HR being 3.33 (95% CI: 2.58-4.30) and 2.08 (95% CI: 1.80-2.41), respectively]. However, we found no interaction effects of AF and PAD on these outcomes.nnnCONCLUSIONSnPAD is an independent risk factor of incident AF but not vice versa. Both PAD and AF are independent risk factors for stroke, heart failure hospitalization, and CV death.