Association of Thromboembolic Risk Score with Left Atrial Thrombus and Spontaneous Echocardiographic Contrast in Non-Anticoagulated Nonvalvular Atrial Fibrillation Patients.

OBJECTIVES: The aim of the study was to examine the association of CHADS2/CHA2DS2-VASc scores with left atrial thrombus (LAT) and spontaneous echocardiographic contrast (SEC) in non-anticoagulated nonvalvular atrial fibrillation (NVAF) spontaneous patients, and to develop a new scoring system for LAT/SEC prediction. METHODS: Consecutive non-anticoagulated NVAF patients with or without LAT/SEC by transesophageal echocardiography were identified in the Guangdong General Hospital. RESULTS: Among 2,173 patients, the prevalence of LAT/SEC was 4.9%. Both predictive values of CHADS2 and CHA2DS2-VASc scores for the presence of LAT/SEC were low-to-moderate (receiver operating characteristic [ROC] = 0.591 and 0.608, respectively, p = 0.90). By multivariate analysis, non-paroxysmal AF, decreased left ventricular ejection fraction, and left atrial enlargement were positively associated with LAT/SEC, while CHADS2/CHA2DS2VASc scores were not. A new scoring system based on these 3 factors above significantly improved the discrimination for LAT/SEC (ROC = 0.792). CONCLUSIONS: CHADS2/CHA2DS2-VASc scores had limited value in predicting LAT/SEC; a new scoring system that combines AF type and echocardiographic parameters may better predict LAT/SEC as a surrogate for cardioembolic risk in NVAF patients.

Assessment of left ventricular twist mechanics by speckle tracking echocardiography reveals association between LV twist and myocardial fibrosis in patients with hypertrophic cardiomyopathy.

We aimed to investigate whether left ventricular (LV) twist analysis can detect the extent of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). This prospective case-control study recruited 81 consecutive patients with HCM examined between January 2012 and April 2013. Data of 76 patients were analyzed after excluding 5 patients whose echocardiographic images were of poor quality. Healthy volunteers (n = 46) served as controls. Both groups underwent comprehensive echocardiographic examination (i.e., Bas-Rotation, AP-Rotation, LVEF, LADs, IVST, LAVi, E/Em, LVMI, advanced LV-twist analysis by speckle tracking echocardiography) and magnetic resonance imaging. Between-group differences were analyzed by independent t test; logistic regression analysis was performed to identify effect factors. No significant differences were found between baseline characteristics of HCM and control groups (all p > 0.05). HCM patients had significantly higher Bas-Rotation, AP-Rotation, LV Twist, LVEF, LADs, IVST, LAVi, E/Em and LVMI than controls (all p < 0.0001) and significantly lower LVDd and E/A (both p < 0.001). Bas-Rotation, AP-Rotation, LV-Twist, LADs, IVST, LAVi, E/Em and LVMI were significantly higher in HCM patients with fibrosis than in those without fibrosis (p < 0.001), but no significant differences in other echocardiographic parameters were found between those with and without fibrosis. Age, Bas-Rotation, AP-Rotation, LV twist, LADs, IVST, LAVi, E/A, E/Em, and LVMI were significant effect factors for fibrosis. AUROC analysis showed that LV twist had high discriminatory power to detect extent of myocardial fibrosis (AUC 0.996, 95 % CI 0.989-1.004, p < 0.001). Left ventricular twist mechanics are associated with the extent of myocardial fibrosis. LV-twist assessment by STE may be clinically useful.

Left atrial minimum volume by real-time three-dimensional echocardiography as an indicator of diastolic dysfunction.

BACKGROUND: Left atrial (LA) maximum volume is becoming a prognostic biomarker for left ventricular (LV) diastolic dysfunction. However, we assessed LV diastolic function by measuring LA phasic volumes using real-time threedimensional echocardiography (RT3DE) in patients with stable coronary artery disease (CAD). METHODS: Sixty-five stable CAD patients with normal LV ejection fraction (LVEF) were divided into three groups according to degree of coronary stenosis: control (n = 15) with <50% stenosis as control group, mildS (n = 25) with mild stenosis (50%-70%) and severeS (n = 25) with >70% stenosis. LA phasic volumes and function were evaluated and compared using RT3DE and two dimensional echocardiography (2DE). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were examined. The correlations of RT3DE-derived parameters with other conventional indices were analyzed. RESULTS: Significant correlations between RT3DE and 2DE for LA volume measurements were: control, r = 0.93; mildS, r = 0.94; severeS, r = 0.90 (all P < 0.05). Patients with severe coronary stenosis presented higher NT-proBNP level, indices of LA minimum volume and volume before atrial contraction, but lower LA total emptying fraction (LAEF) and LAEFpassive. Significant correlations of RT3DE derived LA volume indices with E/E' (r = 0.695) and NF-proBNP (r = 0.630) level were found. CONCLUSIONS: RT3DE derived, LA indices correlate well with NT-proBNP level and may be superior to 2DE measurements for the evaluation of LV diastolic dysfunction. Enlargement of LA minimum volume in stable CAD patients without systolic dysfunction appears earlier and may be better correlated with LV diastolic function than that of LA maximum volume.

Th17 cells contribute to viral replication in coxsackievirus B3-induced acute viral myocarditis.

Acute viral myocarditis (AVMC) is characterized by virus-triggered myocardial inflammation, and Coxsackievirus B3 (CVB3) is the primary pathogen. We previously proved that Th17 cells, besides having proinflammatory effects, were involved in AVMC by enhancing humoral response. However, the relationship between Th17 cells and CVB3 replication remains unknown. In this experiment, we infected BALB/c mice with CVB3 for establishing AVMC models and then found that, with the increase of viral replication, the expressions of splenic Th17 cells, serum IL-17, and cardiac IL-17 mRNA were elevated significantly, accompanied by the progressive cardiac injuries of AVMC. Furthermore, on day 5, the peak time for viral replication, correlation was positive between cardiac IL-17 mRNA and CVB3 RNA (correlation index = 0.835; p < 0.01). Although the expressions of Th1 and CD8(+) T cells, which could secrete the antiviral cytokine IFN-γ and damage the heart, were also elevated, along with Th17 cells, in AVMC, the neutralization of IL-17 further upregulated the percentages of splenic Th1 and CD8(+) T cells and the levels of cardiac IFN-γ mRNA. The cardiac pathological changes were obviously improved after neutralization, with reduced viral replication followed by decreases in the cardiac inflammatory cytokines IL-17, TNF-α, and IL-1ß. These data suggest that Th17 cells contribute to CVB3 replication in AVMC, and that IL-17 might be an important target for regulating the balance of antiviral immunities.

Th17 cells facilitate the humoral immune response in patients with acute viral myocarditis.

BACKGROUND: Recently, the Th17 cell, a newly determined CD4+Th subset, was reported to participate in the inflammation of myocarditis combined with Th1 cells, and this study aimed to explore whether it was involved in the Th2 cell-mediated humoral immunity in viral myocarditis. METHODS: A total of 34 patients, including 16 acute viral myocarditis (AVMC) and 18 dilated cardiomyopathy (DCM) having a history of AVMC, were enrolled for this study besides 18 healthy volunteers. RESULTS: The frequencies of Th17 and Th1 cells, especially Th17 cells in AVMC patients, while those of Th1 and Th2 cells, especially Th2 cells in DCM group, were all increased significantly compared with those in healthy volunteers (P < 0.01), with no changes of Th2 cells in AVMC and Th17 cells in DCM groups. The similar results were also observed in Th cell cytokines (IL-17, INF-gamma, and IL-4) and key transcript factors (RORgammat, T-bet, and GATA-3). Meanwhile, antiheart antibodies (AHA) of IgG type were found in 15 (93.8%) patients with AVMC and ten (55.6%) cases with DCM, accompanied by the higher expression of IL-17R on B cells and the frequencies of B cells than those in healthy controls (P < 0.01 in AVMC and P < 0.05 in DCM, respectively) who had no AHA. Furthermore, both of the B cell activities in AVMC and DCM groups were elevated and positively correlated to serum IL-17 (R = 0.66, P < 0.01) and IL-4 (R = 0.47, P < 0.05) respectively, with no correlation to INF-gamma. CONCLUSIONS: It was Th17 cells but not Th2 cells that helped the B cells to produce AHA in AVMC and not until at the late phase of viral myocarditis could Th2 cells play the important role in mediating humoral response.

Neutralization of IL-17 inhibits the production of anti-ANT autoantibodies in CVB3-induced acute viral myocarditis.

Anti-adenine nucleotide translocator (ANT) autoantibodies are related to the development of Coxsackievirus B3 (CVB3)-triggered acute viral myocarditis (AVMC). Recently, studies suggested that IL-17 especially produced by a novel CD4(+) Th-cell subset Th17 cells contributed to the production of pathogenic autoantibodies in some autoimmune diseases. However, the pathogenic role of IL-17 in AVMC remains largely unknown. In this study, we investigated whether IL-17 was associated with the disease progression and the production of anti-ANT autoantibodies in AVMC mouse model. The results showed that IL-17 monoclonal antibody (mAb)-treated AVMC mice had decreased HW/BW, reduced serum CK-MB activity and improved pathological score of heart sections along with the reduction of circulating IL-17 level and serum anti-ANT autoantibodies. The correlation index of serum IL-17 concentration and anti-ANT-autoantibody level was 0.874, p<0.01. In addition, the experimental results in vitro further proved that IL-17mAb could inhibit the proliferation of CD19(+) B lymphocytes and the secretion of anti-ANT autoantibodies. Our data suggested that IL-17 was related to the disease progression in AVMC mouse model by regulating the production of autoantibodies and blocking IL-17 might represent a promising novel therapeutic approach.