Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35).Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV

Peripartum Serial Echocardiographic Findings in a Patient with Life-threatening Peripartum Cardiomyopathy

A 35-year-old woman was referred to our hospital for the management of acutely decompensated heart failure due to peripartum cardiomyopathy (PPCM). Generally, cardiac examinations are performed after the manifestation of heart failure in patients with PPCM. Thus, reports of serial cardiac examinations before the onset of PPCM are scarce. In this case, we were able to document the serial echocardiographic findings before the onset of life-threatening PPCM. We found that the left ventricular systolic function was preserved at 35 weeks of gestation but declined acutely after delivery at 38 weeks. Although speculative, these findings suggest that left ventricular dilation might precede the onset of PPCM

Presence of increased inflammatory infiltrates accompanied by activated dendritic cells in the left atrium in rheumatic heart disease.

AIMS:Left atrial (LA) structural remodelling develops in rheumatic heart disease (RHD) according to the disease severity of the mitral valve and the presence of atrial fibrillation. Sustained active inflammation has been previously reported in the LA of patients with RHD, suggesting a direct role of cell-mediated immunity in the pathogenesis of LA remodelling. Dendritic cells (DCs) have a major antigen-presenting role, and are known as crucial modulators of innate and adaptive immunity. We investigated whether DCs are involved in the pathogenesis of LA remodelling in RHD. METHODS AND RESULTS:Immunohistochemical analyses were performed using antibodies to CD11c, CD209 and CD80 as markers of myeloid DCs, migratory-active DCs, mature DCs and infiltrated inflammatory cells including T lymphocytes (CD3) and M1 (CD68; pro-inflammatory profile) and M2 (CD163; pro-resolution profile) macrophages. Furthermore, tenascin-C, an extracellular matrix (ECM) protein that appears during ECM remodelling and inflammatory response, was examined. Infiltrated myeloid DCs, migratory-active DCs, mature DCs and other inflammatory infiltrates including T lymphocytes and M1 and M2 macrophages, were significantly higher in the RHD group than the non-RHD group. The positive area fraction for tenascin-C was significantly higher in the RHD group than in the non-RHD group. CONCLUSION:Our histological findings suggest that inflammation may persist long after a bout of rheumatic fever, ultimately leading to ECM remodelling. We identified and quantitatively assessed several subsets of DCs and other immunocompetent cells, and our results indicated that activation of DCs has some role in persistence of LA inflammation in patients with chronic RHD

Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology

Abstract The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF) coactivators, which are highly expressed in the brain. Accordingly, MKL plays important roles in dendritic morphology, neuronal migration, and brain development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are found in patients with schizophrenia and autism spectrum disorder, respectively. Thus, studies on the precise synaptic localisation and function of MKL in neurons are warranted. In this study, we generated and tested new antibodies that specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons. Using these reagents, we biochemically and immunocytochemically show that MKL1 and MKL2 are localised at synapses. Furthermore, shRNA experiments revealed that postsynaptic deletion of MKL1 or MKL2 reduced the percentage of mushroom- or stubby-type spines in cultured neurons. Taken together, our findings suggest that MKL1 and MKL2 are present at synapses and involved in dendritic spine maturation. This study may, at least in part, contribute to better understanding of the molecular mechanisms underlying MKL-mediated synaptic plasticity and neurological disorders

Retracted: Effects of cardiac resynchronization therapy in patients with inotrope‐dependent class IV end‐stage heart failure

Abstract Background Cardiac resynchronization therapy (CRT) has been widely used for the treatment of refractory heart failure (HF). However, the efficacy of CRT is not well established in class IV HF patients on inotropic support. Methods Twenty‐six patients (age 55±18 years, 73% men) with inotrope‐dependent HF were reviewed to evaluate the effectiveness of CRT in class IV HF patients on inotropic support. Results Intravenous inotropic therapy was administered for 72±56 days before CRT and consisted of dobutamine (n=24; 3.0±1.2 μg kg−1 min−1), dopamine (n=2; 4.5±2.1 μg kg−1 min−1), and/or milrinone (n=16; 0.12±0.09 μg kg−1 min−1). CRT did not produce significant reverse remodeling in eligible patients (left ventricular ejection fraction 23±7% to 25±9%; p=0.23, left ventricular end‐diastolic diameter 70±9 mm to 68±9 mm; p=0.14). After CRT device implantation, 13 (50%) patients experienced 1 or more episodes of ventricular tachyarrhythmia or sudden cardiac death. Twenty (77%) patients survived to hospital discharge with weaning from inotropic support (70±70 days after CRT implantation). The 1‐year survival rate was 81%. However, data from long‐term follow‐up showed that 68% of the study patients who attained survival discharge had an HF hospitalization event within the follow‐up period. Conclusion CRT did not result in significant reverse remodeling in patients with inotrope‐dependent class IV end‐stage HF. However, it contributed to dramatically improve the cardiovascular outcomes at least in the short‐term period in some patients

Multivariate linear regression analysis of aortic valvular fibrosis in patients with severe AS.

<p>Multivariate linear regression analysis of aortic valvular fibrosis in patients with severe AS.</p