Predominant determinants for evaluation of right parasternal approach in transthoracic echocardiography in aortic stenosis: a study based on three-dimensional cardiac computed tomography analysis.

The maximum blood flow velocity through the aortic valve (AVmax) using Doppler transthoracic echocardiography (TTE) is important in assessing the severity of aortic stenosis (AS). The right parasternal (RP) approach has been reported to be more useful than the apical approach, but the anatomical rationale has not been studied. We aimed to clarify the influence of the angle formed by the ascending aorta and left ventricle on Doppler analysis by TTE (Sep-Ao angle) and three-dimensional multidetector computed tomography (3D-MDCT) in patients with AS. A total of 151 patients evaluated using the RP approach and 3D-MDCT were included in this study. The Sep-Ao angle determined using TTE was compared with that determined using 3D-MDCT analysis. In MDCT analysis, the left ventricular (LV) axis was measured in two ways and the calcification score was calculated simultaneously. The Sep-Ao angle on TTE was consistent with that measured using 3D-MDCT. In patients with an acute Sep-Ao angle, the Doppler angle in the apical approach was larger, potentially underestimating AVmax. Multivariate analysis revealed that an acute Sep-Ao angle, large Doppler angle in the apical approach, smaller Doppler angle in the RP approach, and low aortic valve calcification were independently associated with a higher AVmax in the RP approach than in the apical approach. The Sep-Ao angle measured using TTE reflected the 3D anatomical angle. In addition to measurements using the RP approach, technical adjustments to minimize the Doppler angle to avoid bulky calcification should always be noted for accurate assessment.

Lack of Herpes Virus Entry Mediator Signals in Thymocytes Impairs Conventional CD8 T Cell Selection and Promotes Memory-like CD8 T Cell Development.

Thymocytes having diverse Ag specificities are selected in response to self-MHC-peptide expressed in thymic epithelial cells, which contributes to the formation of a T cell repertoire. However, it is not well understood whether additional signals from epithelial cells are required to drive positive selection. In this study, we found that one of the TNFR superfamily members, herpes virus entry mediator (HVEM), when expressed on thymocytes provides signals for positive selection. HVEM deficiency in double-positive (DP) thymocytes impaired positive selection of CD8 thymocytes. HVEM-deficient thymocytes in OT-1 TCR transgenic mice exhibited significant defects in positive selection and impaired CD69 upregulation of selected thymocytes. HVEM ligands (lymphotoxin-like, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes, and B and T lymphocyte attenuator) were expressed in cortical thymic epithelial cells. Weak TCR ligation combined with HVEM signals enhanced ERK activation in DP thymocytes developed in vitro. Insufficient signals for positive selection in HVEM-deficient DP thymocytes led to the development of innate memory-like CD8 T cells expressing high levels of CD122, along with the increased development of PLZF+ NKT cells. These results suggest that thymocytes receive activation signals through HVEM during positive selection. Thus, our findings provide evidence that the threshold of thymocyte positive selection is set by signals from TCR in association with HVEM.

Right ventricular contractility affects the clinical efficacy of add-on tolvaptan following hospitalization for heart failure in patients with significant tricuspid regurgitation.

Tricuspid regurgitation (TR) is a common condition that is independently associated with high mortality rates in patients with heart failure (HF). Several studies have demonstrated the clinical efficacy of add-on tolvaptan in patients hospitalized for HF. However, the effects of add-on tolvaptan in patients with significant TR are less well understood. Among the patients with moderate-to-severe TR assessed by transthoracic echocardiography during hospitalization for congestive HF, 39 patients who could complete the clinical course after starting add-on tolvaptan were included in the study. Rehospitalization due to HF and cardiac death were defined as adverse cardiac events in this study. We investigated the presence or absence of cardiac events within 2 years following the introduction of tolvaptan and evaluated echocardiographic functional parameters associated with cardiac events. The average patient age was 75 ± 14 years, and 23 patients (59%) experienced adverse cardiac events within 2 years after add-on tolvaptan administration. Serum creatinine (mg/dL) and brain natriuretic peptide (pg/mL) concentrations at discharge were significantly higher in patients with cardiac events than in those without cardiac events {1.48 [1.02-1.58] vs. 1.07 [0.79-1.41], p = 0.03; 526 [414-1044] vs. 185 [104-476], p = 0.01, respectively}. The presence or absence of past hospitalization for HF was also significantly higher in the event-positive group compared to event-free group (78 vs. 44%, p = 0.04). Comparison of echocardiographic parameters revealed that patients with cardiac events had a significantly lower left ventricular ejection fraction (40 ± 16 vs. 49 ± 15%, p = 0.049) and lower right ventricular fractional area change (RVFAC) (35 ± 12 vs. 45 ± 10%, p = 0.008) than those without cardiac events. Multiple logistic regression analysis revealed that RVFAC and past hospitalization for HF were independently associated with cardiac events following the introduction of tolvaptan (odds ratio, 0.934 and 4.992; p = 0.048 and 0.04, respectively). Right ventricular contractility as well as past history of admission for HF, left ventricular ejection fraction, renal function, and brain natriuretic peptide level at discharge may reflect the clinical outcomes after HF hospitalization in patients with significant TR who were treated with tolvaptan.